p53 regulates primordial follicle activation through the mTOR signaling pathway / 生理学报

This paper aimed to investigate the role and potential mechanism of p53 on primordial follicle activation. Firstly, the p53 mRNA expression in the ovary of neonatal mice at 3, 5, 7 and 9 days post-partum (dpp) and the subcellular localization of p53 were detected to confirm the expression pattern of p53. Secondly, 2 dpp and 3 dpp ovaries were cultured with p53 inhibitor Pifithrin-μ (PFT-μ, 5 μmol/L) or equal volume of dimethyl sulfoxide for 3 days. The function of p53 in primordial follicle activation was determined by hematoxylin staining and whole ovary follicle counting. The proliferation of cell was detected by immunohistochemistry. The relative mRNA levels and protein levels of the key molecules involved in the classical pathways associated with the growing follicles were examined by immunofluorescence staining, Western blot and real-time PCR, respectively. Finally, rapamycin (RAP) was used to intervene the mTOR signaling pathway, and ovaries were divided into four groups: Control, RAP (1 μmol/L), PFT-μ (5 μmol/L), PFT-μ (5 μmol/L) + RAP (1 μmol/L) groups. The number of follicles in each group was determined by hematoxylin staining and whole ovary follicle counting. The results showed that the expression of p53 mRNA was decreased with the activation of primordial follicles in physiological condition. p53 was expressed in granulosa cells and oocyte cytoplasm of the primordial follicles and growing follicles, and the expression of p53 in the primordial follicles was higher than that in the growing follicles. Inhibition of p53 promoted follicle activation and reduced the primordial follicle reserve. Inhibition of p53 promoted the proliferation of the granulosa cells and oocytes. The mRNA and protein expression levels of key molecules in the PI3K/AKT signaling pathway including AKT, PTEN, and FOXO3a were not significantly changed after PFT-μ treatment, while the expression of RPS6/p-RPS6, the downstream effectors of the mTOR signaling pathway, was upregulated. Inhibition of both p53 and mTOR blocked p53 inhibition-induced primordial follicle activation. Collectively, these findings suggest that p53 may inhibit primordial follicle activation through the mTOR signaling pathway to maintain the primordial follicle reserve.

Transition of autophagy and apoptosis in fibroblasts depends on dominant expression of HIF-1α or p53 / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

It has been revealed that hypoxia is dynamic in hypertrophic scars; therefore, we considered that it may have different effects on hypoxia-inducible factor-1α (HIF-1α) and p53 expression. Herein, we aimed to confirm the presence of a teeterboard-like conversion between HIF-1α and p53, which is correlated with scar formation and regression. Thus, we obtained samples of normal skin and hypertrophic scars to identify the differences in HIF-1α and autophagy using immunohistochemistry and transmission electron microscopy. In addition, we used moderate hypoxia in vitro to simulate the proliferative scar, and silenced HIF-1α or p53 gene expression or triggered overexpression to investigate the changes of HIF-1α and p53 expression, autophagy, apoptosis, and cell proliferation under this condition. HIF-1α, p53, and autophagy-related proteins were assayed using western blotting and immunofluorescence, whereas apoptosis was detected using flow cytometry analysis, and cell proliferation was detected using cell counting kit-8 (CCK-8) and 5-bromo-2'-deoxyuridine (BrdU) staining. Furthermore, immunoprecipitation was performed to verify the binding of HIF-1α and p53 to transcription cofactor p300. Our results demonstrated that, in scar tissue, HIF-1α expression increased in parallel with autophagosome formation. Under hypoxia, HIF-1α expression and autophagy were upregulated, whereas p53 expression and apoptosis were downregulated in vitro. HIF-1α knockdown downregulated autophagy, proliferation, and p300-bound HIF-1α, and upregulated p53 expression, apoptosis, and p300-bound p53. Meanwhile, p53 knockdown induced the opposite effects and enhanced HIF-1α, whereas p53 overexpression resulted in the same effects and reduced HIF-1α. Our results suggest a teeterboard-like conversion between HIF-1α and p53, which is linked with scar hyperplasia and regression.

Shexiang Baoxin Pill Regulates Intimal Hyperplasia, Migration, and Apoptosis after Platelet-Derived Growth Factor-BB-Stimulation of Vascular Smooth Muscle Cells via miR-451 / 中国结合医学杂志

OBJECTIVE@#To investigate the regulatory roles of Shexiang Baoxin Pill (SXBXW) in neointimal formation and vascular smooth muscle cells (VSMCs) invasion and apoptosis as well as the potential molecular mechanisms using cultured VSMCs model of vascular injury (platelet-derived growth factor (PDGF)-BB-stimulated) in vitro.@*METHODS@#VSMCs were randomly assigned to 5 groups: blank, PDGF-BB (20 ng/mL+ 0.1% DMSO), SXBXW-L (PDGF-BB 20 ng/mL + SXBXW low dose 0.625 g/L), SXBXW-M (PDGF-BB 20 ng/mL + SXBXW medium dose 1.25 g/L) and SXBXW-H (PDGF-BB 20 ng/mL+ SXBXW high dose 2.5 g/L) group. Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay and bromodeoxyuridine (BrdU) incorporation assay, the migration effects were detected by Transwell assay, cell apoptosis rate was measured by the Annexin V/propidium iodide (PI) apoptosis kit. The markers of contractile phenotype of VSMCs were detected with immunofluorescent staining. To validate the effects of miR-451 in regulating proliferation, migration and apoptosis treated with SXBXW, miR-451 overexpression experiments were performed, the VSMCs were exposed to PDGF-BB 20 ng/mL + 0.1% DMSO and later divided into 4 groups: mimic-NC (multiplicity of infection, MOI=50), SXBXW (1.25 g/L) + mimic-NC, mimic-miR451 (MOI=50), and SXBXW (1.25 g/L) + mimic-miR451, and alterations of proteins related to the miR-451 pathway were analyzed using Western blot.@*RESULTS@#PDGF-BB induced VSMCs injury causes acceleration of proliferation and migration. SXBXW inhibited phenotypic switching, proliferation and migration and promoted cell apoptosis in PDGF-BB-induced VSMCs. In addition, miR-451 was shown to be down-regulated in the VSMCs following PDGF-BB stimulation. SXBXW treatment enhanced the expression of miR-451 in PDGF-BB-induced VSMCs (P<0.05). Compared with SXBXW + mimic-NC and mimic-miR451 groups, the expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (Ywhaz) and p53 was further reduced in SXBXW + mimic-miR451 group, while activating transcription factor 2 (ATF2) was increased in VSMCs (P<0.05).@*CONCLUSION@#SXBXW regulated proliferation, migration and apoptosis via activation of miR-451 through ATF2, p53 and Ywhaz in PDGF-BB-stimulated VSMCs.

Oxidative Damage to BV2 Cells by Trichloroacetic Acid: Protective Role of Boron via the p53 Pathway / 生物医学与环境科学（英文）

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.

Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN / 国际口腔科学杂志·英文版

Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.

Extract from Zanthoxylum piperitum Induces Apoptosis of AGS Gastric Cancer Cells Through Akt/MDM2/p53 Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To determine the effect of Zanthoxylum piperitum extracet (ZPE) on apoptosis and analyze anticancer substances in ZPE, changes in proteins related to apoptosis, and pathological changes in tumors in mouse.@*METHODS@#Fifteen 4-week-old female BALB/c nu/nu mice were divided into 3 groups depending on ZPE dose, with 5 in each group. AGS gastric carcinoma cells (1 × 10@*RESULTS@#High performance liquid chromatography (HPLC) analysis showed that ZPE contained organic sulfur compounds such as alliin and S-allylcysteine. MTT assay results revealed that ZPE (10-85 µ g/mL) could effectively inhibit the growth of AGS gastric cancer cells at higher concentrations (P<0.05, P<0.01). The annexin V & dead cell staining assay and cell cycle arrest assay confirmed a dose-dependent increase in the apoptosis rate and G@*CONCLUSION@#ZPE decreases AGS cell proliferation and induces apoptosis by inhibiting Akt and MDM2 expression.

Inmunohistoquímica de p16 y p53 en cáncer de vulva / Immunohistochemistry of p16 and p53 in vulvar cancer

El carcinoma escamoso vulvar puede desarrollarse de manera asociada o independiente a la infección por HPV. La relación entre la patogénesis, la clasificación, el perfil inmunohistoquímico, y el pronóstico ha sido estudiada con algunas discrepancias. El objetivo del trabajo fue observar la concordancia clásicamente descripta que asocia a los carcinomas queratinizantes con la ausencia de infección por HPV y a los carcinomas warty y basaloides con la presencia de dicho virus. Para ello, revisamos la clínica, la morfología y el inmunofenotipo de 39 casos de nuestro hospital. Los tumores fueron clasificados histológicamente en carcinomas escamosos queratinizantes clásicos (30), warty (5) y basaloides (4). En el análisis estadístico la expresión de p16 fue asociada de manera significativa con una edad menor al momento del diagnóstico (p = 0.0025), presencia de lesión intraepitelial escamosa de alto grado (p < 0.0001), coilocitosis (p = 0.02), y subtipo morfológico (p = 0.02); y fue inversamente asociado con la expresión de p53 (p < 0.0001) y con el liquen escleroso (p = 0.0051). Resulta peculiar que, de los casos estudiados, 4 carcinomas queratinizantes coexpresaron p16 y p53. Un solo tumor de tipo warty resultó negativo para p16 y positivo para p53, y 9 queratinizantes resultaron positivos para p16 y negativos para p53. Si bien estos hallazgos indican que con la sola utilización de la hematoxilina y eosina podrían definirse de manera correcta los tumores asociados al HPV, sugerimos fuertemente la realización de inmunohistoquímica, especialmente en carcinomas escamosos queratinizantes en pacientes jóvenes o con historia de HPV.

Squamous cell carcinoma of the vulva may develop in association or independently of HPV infection. The relationship between pathogenesis, classification, immunohistochemical profile and prognosis has been studied in the literature with some discrepancies. The aim of this study was to observe the classical association of keratinizing carcinomas with the absence of HPV infection and warty and basaloid carcinomas with the presence of this virus. Therefore, we reviewed the clinic, morphology, and immunophenotype of 39 cases. The tumors were histologically classified into classic keratinizing squamous carcinoma (30), warty (5) and basaloid (4). In the statistical analysis, diffuse expression with p16 was significantly associated with younger age (p = 0.0025), presence of high-grade intraepithelial lesion (p < 0.0001), koilocytosis (p = 0.02), and morphological subtype (p = 0.02), and was inversely associated with the expression of p53 (p < 0.0001) and the presence of lichen sclerosus (p = 0.0051). It is curious that 4 keratinizing carcinomas of the cases studied presented coexpression of p16 and p53. Only one warty tumor was negative for p16 and positive for p53, and 9 keratinizing tumors were positive for p16 and negative for p53. Although these findings show that the use of hematoxylin and eosin could correctly define tumors associated with HPV, we strongly suggest the performance of immunohistochemistry, especially in squamous keratinizing classic carcinomas in young patients with a history of HPV.

Relationship between p53 rs1625895 polymorphism and prognosis in diffuse large B-cell lymphoma / 北京大学学报(医学版)

OBJECTIVE@#p53 gene, as "the guardian of the genome", is the most widely studied tumor suppressor gene. Previous studies have shown that about 50 percent of tumors have P53 dysfunction. This article aims to retrospectively analyze the correlation between p53 rs1625895 polymorphism and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#PCR combined with Sanger sequencing were used to detect rs1625895 genotype in 384 DLBCL patients. The relationship between rs1625895 polymorphisms and the clinical characteristics, first-line therapeutic effects and the prognosis of the patients were analyzed.@*RESULTS@#Among all the patients, 2 (0.5%) patients with AA genotype, 34 (8.9%) patients with AG genotype and 348 (90.6%) patients with GG genotype were identified. The patients with different rs1625895 genotypes did not have any difference in terms of age, gender, B symptoms (developing any of the following symptoms: unexplained recurrent fever (often above 38 °C), night sweats, and unexplained weight loss of 10% within 6 months ), erythrocyte sedimentation rate (ESR), international prognostic index (IPI) and molecular subtype (P>0.05). The overall response rate (ORR) was 82.9% and 82.8% in AA/AG and GG, respectively. There was no significant difference between the first-line therapeutic effects of the two groups (P>0.05). And there was also no difference between A allele carriers and homozygous G allele carriers for the 5-year progressionfree survival rate (PFS) (71.8% vs. 62.3%, χ2=1.351, P=0.245) and 5-year overall survival rate (OS) (72.2% vs. 64.1%, χ2=1.267, P=0.260). But in the subgroup with Germinal Center B-cell (GCB) type, the patients carrying A allele for rs1625895 had an obviously longer PFS (91.7% vs. 72.7%, χ2=4.493, P=0.034) and OS (91.7% vs. 76.7%, χ2=4.246, P=0.039) compared with the patients homozygous for the G allele. As for the patients with non-GCB subtype, there was no significant difference in PFS and OS between different rs1625895 genotypes (P>0.05). According to whether the first-line regimen contained rituximab or not, the patients were divided into two groups treated with cyclophosphoramide, doxorubicin, vincristine and prednisone (CHOP) or with rituximab and CHOP (R-CHOP). But in both subgroups, there was no significant difference in the 5-year PFS and OS between the AA/AG and GG patients, too (P>0.05).@*CONCLUSION@#For DLBCL patients receiving CHOP regimen chemotherapy in the first line, p53 rs1625895 cannot predict the clinical efficacy and prognosis of the patients, but in the patients with GCB subtype, this polymorphism may be a prognostic indicator.

Icariin reduces human colon carcinoma cell growth and metastasis by enhancing p53 activities

Icariin has been reported to possess high anticancer activity. Colon carcinoma is one of the leading causes of cancer-related mortality worldwide. Here, the anticancer activity of icariin against HCT116 colon carcinoma cells and the possible underlying mechanism were studied. The trypan blue staining assay, wound healing assay, clonogenic assay, CCK-8 assay, and Annexin V-FITC/PI double staining method were carried out to determine the changes of HCT116 cell growth and migration. mRNA and protein expressions were determined by quantitative real-time PCR and western blot, respectively. Moreover, small interfering RNA (siRNA) plasmid was used to examine the role of p53 in icariin-induced apoptosis in HCT116 cells. Icariin significantly suppressed colon carcinoma HCT116 cells by decreasing migration and viability, and simultaneously promoting apoptosis. Icariin exerted the anti-tumor effect in a dose-dependent manner by up-regulating p53. During treatment of icariin, p-p53, p21, and Bax levels increased, and Bcl-2 level decreased. Short time treatment with icariin induced DNA damage in HCT116 cells. Furthermore, the cytotoxicity of icariin was decreased after p53 knockdown or by using caspase inhibitors. p53 was involved in activities of caspase-9 and caspase-3. Icariin repressed colon carcinoma cell line HCT116 by enhancing p53 expression and activating p53 functions possibly through Bcl-2/Bax imbalance and caspase-9 and -3 regulation. Icariin treatment also induced DNA damage in HCT116 cells.

Caracterização dos fenótipos de mucina podem prever a recorrência do câncer gástrico precoce após a mucosectomia endoscópica / Characterization of the mucin phenotype can predict gastric cancer recurrence after endoscopic mucosal resection

ABSTRACT BACKGROUND: Endoscopic mucosal resection is still considered an accepted treatment for early gastric cancer for selected cases. Histopathologic criteria for curative endoscopic resection are intramucosal well-differentiated adenocarcinoma, lateral and deep margins free of tumor, no histological ulceration, and no venous or lymphatic embolism. A 5% local recurrence rate has been described even when all the above-mentioned criteria are met. On the other hand, antigen expression by tumoral cells has been related to the biological behavior of several tumors. OBJECTIVE: To evaluate whether early gastric cancer mucin immunoexpression, p53 and Ki-67, can predict recurrence after endoscopic mucosal resection, even when standard histopathologic criteria for curative measures have been attempted. METHODS: Twenty-two patients with early gastric cancer were considered to have been completely resected by endoscopic mucosal resection. Local recurrence occurred in 5/22 (22.7%). Immunohistochemical study was possible in 18 (81.8%) resected specimens. Patients were divided in two groups: those with and those without local recurrence. They were compared across demographic, endoscopic, histologic data, and immunohistochemical factors for MUC2, MUC5a, CD10, p53, and Ki-67. RESULTS: Mucin immunoexpression allowed a reclassification of gastric adenocarcinoma in intestinal (10), gastric (2), mixed (4), and null phenotypes (2). Mixed phenotype (positive for both MUC2 and MUC5a) was found in 80% of cases in the local recurrence group, while the intestinal type (positive MUC2 and negative MUC5a) was found in 76.9% of cases without local recurrence (P=0.004). Other observed features did not correlate with neoplastic recurrence. CONCLUSION: The mixed phenotype of early gastric adenocarcinoma is associated with a higher probability of local recurrence after endoscopic mucosal resection.

RESUMO CONTEXTO: A ressecção endoscópica da mucosa é tratamento aceito para o tratamento do câncer gástrico precoce em casos selecionados. Os critérios histopatológicos favoráveis à ressecção endoscópica curativa são adenocarcinomas intramucosos, bem diferenciados, com margens lateral e profunda livres, ausência de ulceração ou de embolização angiolinfática. Taxas de recorrência local próximas a 5% têm sido descritas mesmo quando se cumprem tais critérios. Por outro lado, a expressão antigênica por células tumorais tem sido relacionada com o comportamento biológico de diversos tumores. OBJETIVO: Avaliar se a imunoexpressão de mucinas, p53 e Ki-67 podem predizer a recorrência tumoral após mucosectomia endoscópica no câncer gástrico precoce, mesmo se critérios de cura histopatológicos forem atingidos. MÉTODOS: Vinte e dois pacientes com critérios de cura para ressecção endoscópica e sumetidos a mucosectomia foram selecionados. A recorrência local ocorreu em 5/22 (22,7%). O estudo imunohistoquímico foi realizado em 18 (81,8%) espécimens. Os pacientes foram divididos em grupos com e sem recorrência local. Foram comparados quanto a dados demográficos, endoscópicos, histológicos e fatores imunohistoquímicos para MUC2, MUC5A, CD10, p53, e Ki-67. RESULTADOS: A imunoexpressão de mucinas permitiu a reclassificação dos adenocarcinomas gástricos em intestinal (10), gástrico (2), e de fenótipo misto (4) e nulo (2). Os fenótipos mistos (positivos tanto para MUC2 quanto para MUC5A) foram encontrados em 80% dos casos no grupo de recorrência local, enquanto tipos intestinais (MUC2 positivo e MUC5A negativo) foram identificados em 76,9% dos casos sem recorrência (P=0,004). Os outros fatores observados não se relacionaram com a recorrência tumoral. CONCLUSÃO: O fenótipo misto do câncer gástrico precoce está associado a maior probabilidade de recorrência local após a mucosectomia.

Post-immunization immunohistochemical expression of Caspase 3 and p53 apoptotic markers in experimental hydatidosis / Expressão imuno-histoquímica de marcadores de apoptose Caspase 3 e p53 pós-imunização em hidatidose experimental

Abstract The aim of this study was to investigate post-immunization apoptotic changes in experimental hydatidosis, using Caspase 3 and p53 immunohistochemical markers. Two groups of rabbits were immunized with a crude antigen (group 1) or a partially purified antigen (group 2) and were compared to an infected non-immunized control group. More effective immune responses were obtained in group 2 than group 1, signified by fewer and smaller cystic lesions and more severe destructive changes. Normal growth of cysts was attained in the control group, with no expression of apoptotic markers. Significantly higher expression of Caspase 3 and p53 were observed in group 1 compared to group 2, as indicated by OD and area percentage, respectively (Group 1 Caspase 3: 0.89±0.21, 93.5%±6.2; Group 1 p53: 0.46±0.18, 53.26%±11.6; Group 2 Caspase 3: 0.52±0.15, 49.23%±11.7; Group 2 p53: 0.19±0.4, 18.17%±7.3). Vaccine-induced immune responses and cellular damage may underlie the expression of apoptotic markers that appeared to result in a degenerative and atrophic course of action upon immunization. The results of the current study emphasize the importance of immunization for the stimulation of protective immune responses and in preventing mechanisms of evasion to ensure normal cell growth. A cost/benefit control program that implements proper vaccine preparations should be further assessed for complete elimination of severe infections in endemic areas.

Resumo O objetivo do presente estudo foi investigar mudanças de apoptose pós-imunização em hidatidose experimental, usando os marcadores imuno-histoquímicos Caspase 3 e p53. Dois grupos de coelhos foram imunizados com antígeno bruto (grupo 1) e com antígeno parcialmente purificado (grupo 2). Estes grupos foram comparados a um grupo controle infectado e não-imunizado. Respostas imunes mais eficientes foram obtidas do grupo 2, que apresentou lesões císticas menores e menos frequentes, e mudanças destrutivas mais graves. Cistos cresceram normalmente no grupo controle, sem expressão dos marcadores de apoptose. Expressões significativamente mais altas de Caspase 3 e p53 foram observadas no grupo 1 quando comparado ao grupo 2, como indicado por DO e área de percentagem, respectivamente (Grupo 1 Caspase 3: 0,89±0,21, 93,5%±6,2; Grupo 1 p53: 0,46±0,18, 53,26%±11,6; Grupo 2 Caspase 3: 0,52±0,15, 49,23%±11,7; Grupo 2 p53: 0,19±0,4, 18,17%±7,3). Respostas imunológicas induzidas por vacinas e danos celulares podem ser a base para a expressão dos marcadores de apoptose cujos desfechos demonstraram ação degenerativa e atrófica durante imunização. Os resultados do presente estudo enfatizam a importância da imunização para o estímulo de respostas imunes de proteção e para mecanismos de prevenção de evasão para garantir crescimento celular normal. Um programa de controle de custo/benefício que implemente preparações de vacinas adequadas deve ser analisado em mais detalhe para a completa eliminação de infecções graves em áreas endêmicas.

Evaluation of microvessel density and p53 expression in pancreatic adenocarcinoma

OBJECTIVE: To evaluate the prognostic significance of microvessel density and p53 expression in pancreatic cancer. METHODS: Between 2008 and 2012, 49 patients with pancreatic adenocarcinoma underwent resection with curative intention. The resected specimens were immunohistochemically stained with anti-p53 and anti-CD34 antibodies. Microvessel density was assessed by counting vessels within ten areas of each tumoral section a highpower microscope. RESULTS: The microvessel density ranged from 21.2 to 54.2 vessels/mm2. Positive nuclear staining for p53 was found in 20 patients (40.6%). The overall median survival rate after resection was 24.1 months and there were no differences in survival rates related to microvessel density or p53 positivity. Microvessel density was associated with tumor diameter greater than 3.0 cm and with R0 resection failure. CONCLUSIONS: Microvessel density was associated with R1 resection and with larger tumors. p53 expression was not correlated with intratumoral microvessel density in pancreatic adenocarcinoma.

Sonography of Invasive Apocrine Carcinoma of the Breast in Five Cases

OBJECTIVE: To evaluate the sonographic features of invasive apocrine carcinoma (IAC) of the breast. MATERIALS AND METHODS: This study included five pathologically proven cases of IAC, and their sonographic features were retrospectively analyzed according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon. RESULTS: All five lesions involved the left breast and were seen as irregularly shaped masses. All lesions, except one, had a parallel orientation to the chest wall. All five lesions showed noncircumscribed margins and heterogeneous echotexture; however, they showed various posterior features. One lesion had edema as an associated feature. Sonographic assessments were classified as BI-RADS category 4 in all five cases. CONCLUSION: Invasive apocrine carcinoma sonographic findings are difficult to differentiate from those of invasive ductal carcinoma of no special type.

Anthocyanin Induces Apoptosis of DU-145 Cells In Vitro and Inhibits Xenograft Growth of Prostate Cancer

PURPOSE: To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model). MATERIALS AND METHODS: The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2x106) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated. RESULTS: Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth. CONCLUSION: This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model.

P53 expression in hepatocellular carcinoma: influence on the radiotherapeutic response of the hepatocellular carcinoma

No abstract available.

Influence of P53 on the radiotherapy response of hepatocellular carcinoma

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines. METHODS: Western blotting was used to measure P53 expression. The effects of radiotherapy with iodine-131 were assessed by using the clonogenic assay to evaluate cell survival. Flow cytometry was carried out to examine the effects of iodine-131 on cell death, oxidative stress, reduced intracellular glutathione expression, the mitochondrial membrane potential, and the cell cycle. RESULTS: The P53 protein was not expressed in Hep3B2.1-7 cells, was expressed at normal levels in HepG2 cells, and was overexpressed in HuH7 cells. P53 expression in the HuH7 and HepG2 cell lines increased after internal and external irradiation with iodine-131. Irradiation induced a decrease in cell survival and led to a decrease in cell viability in all of the cell lines studied, accompanied by cell death via late apoptosis/necrosis and necrosis. Irradiation with 131-iodine induced mostly cell-cycle arrest in the G0/G1 phase. CONCLUSIONS: These results suggest that P53 plays a key role in the radiotherapy response of HCC.

CD34 and p53 Immunohistochemical Stains Differentiate Hypocellular Myelodysplastic Syndrome (hMDS) from Aplastic Anemia and a CD34 Immunohistochemical Stain Provides Useful Survival Information for hMDS

BACKGROUND: The presence of significant dysplasia in bone marrow (BM) aspirates helps to distinguish between hypocellular myelodysplastic syndrome (hMDS) and aplastic anemia (AA). Occasionally, diluted BM aspirates make it difficult to recognize dysplastic changes and can also negatively affect the detection of cytogenetic abnormalities in hMDS. We evaluated the usefulness of CD34 and p53 immunoreactivity for discriminating between hMDS and AA and for estimating survival outcomes in hMDS patients. METHODS: BM clot section (BMC) or BM biopsy (BMB) specimens were obtained from 64 hMDS/AA patients (33 with hMDS and 31 with AA) and seven controls. Immunohistochemical (IHC) staining for CD34 and p53 was performed by using the EnVision detection system (Dako, Denmark). We compared the results of IHC staining, BM findings, and chromosomal analyses, and determined overall survival outcomes. RESULTS: The number of CD34- and p53-positive BM cells was higher among the patients with hMDS than among the patients with AA (P<0.001 and P=0.001, respectively). hMDS patients with increased CD34-positive cells had significantly poorer survival outcomes compared with those with normal number of CD34-positive cells (P=0.013). CONCLUSIONS: CD34 and p53 IHC stains of BMC or BMB provide useful information for differentiating between hMDS and AA. CD34 IHC staining of BMC or BMB also provides useful information for estimating survival outcomes in hMDS patients.

Prognostic Significance of p53, mTOR, c-Met, IGF-1R, and HSP70 Overexpression after the Resection of Hepatocellular Carcinoma

BACKGROUND/AIMS: The current study examines the expression of molecular biomarkers in hepatocellular carcinoma (HCC) and whether these findings correlate with the clinicopathologic features of the disease and patient survival. METHODS: We analyzed the immunohistochemical expression of p53, mammalian target of rapamycin (mTOR), c-Met, and insulin-like growth factor 1 receptor (IGF-1R) heat shock protein 70 (HSP70) with the clinicopathologic features of 83 HCCs. RESULTS: p53 expression was higher in the male patients with undifferentiated histological tumor grades, cirrhosis, and portal vein invasion. High 48 c-Met expression correlated with cirrhosis, and high mTOR expression correlated with the tumor grade and cirrhosis. High IGF-1R expression correlated with the tumor grade and cirrhosis. A multivariate analysis identified a significant relationship between the high expression of p53, tumor grade, and portal vein invasion. In addition, a high expression of mTOR was related to tumor grade and cirrhosis, and a high expression of HSP70 was related to portal vein invasion in a multivariate analysis. The Kaplan-Meier survival curve for patients with high versus low Edmondson grades and p53 expression was statistically significant. CONCLUSIONS: p53, mTOR, and IGF-1R expression correlated with the Edmondson tumor grade in a univariate analysis, while p53 and mTOR correlated with the Edmondson tumor grade in a multivariate analysis. In addition, the tumor grade was found to predict survival. p53 was primarily related to the clinicopathologic features compared to other markers, and it is a poor prognostic factor of survival.

A Case of Metachronous Development of Esophageal Squamous Cell Carcinoma in the Patient with Esophageal Carcinosarcoma / 대한소화기학회지

Esophageal carcinosarcoma is a rare malignant esophageal neoplasm consisting of both carcinomatous and sarcomatous elements, with an incidence of 0.5%. There have been only a few case reports of carcinosarcoma and squamous cell carcinoma coexisting in the esophagus. However, all of these are cases of synchronous or metachronous development of carcinosarcoma after chemoradiotherapy in patients of esophageal squamous cell carcinoma. A 53-year-old man underwent esophagogastroduodenoscopy because of chest pain for several months. Endoscopic examination revealed a huge pedunculated esophageal polypoid mass. Endoscopic submucosal dissection (ESD) was performed and histopathologic examination confirmed spindle cell carcinoma (carcinosarcoma). He refused additional esophagectomy. After 21 months, third follow-up endoscopy showed poorly-demarcated flat, faint discolored lesions at different location from the previous ESD site and endoscopic biopsies confirmed squamous cell carcinoma. To the best of our knowledge, this is the first case of metachronous development of esophageal squamous cell carcinoma in a patient with esophageal carcinosarcoma.

expression of P53 in non small cell lung cancer

Despite major advances in cancer treatment in the past two decades, the prognosis of patients with lung cancer has improved only minimally. Although tumor stage is the most significant prognostic factor, the variation in survival within staging groups requires information about additional factors influencing the outcome. Among several genetic aberrations that have been implicated in lung cancer, mutations in the p53 gene are the most common. The aim of this study was to evaluate the expression of p53 in non-small cell lung cancer. To correlate the relation of p53 with some clinico-pathological parameters. And to compare the results with that of others. Tumor tissues from 52 patients with non small cell lung cancer [NSCLC] were assessed by immune-histochemistry for the expression of p53. The immunohistochemical study was performed on formalin-fixed, paraffin-embedded sections using LSAB immune-peroxidase method. Thirty nine [75%] of 52 patients revealed aberrant immunostaining for p53. No significant relation was observed between the p53 and patient age [P=0.596]. A significant association [P=0.048] was found between the p53 and the sex of the patient with higher expression in males and the p53 was significantly [P=0.0345] associated with histopathological type of tumor. Comparing p53 expression with grade resulted in a strong positive correlation [P= 0.0002]. The percentage of p53-positive tumors progressively increased from [2.56%] in well differentiation to [53.85%] in poorly differentiated tumor. P53 was significantly association with sex, grade and histological type, the detection of p53 may be important marker to predict the prognosis of the patients with NSCLC and for stratifying these patients into more accurate prognostic group.